The human papilloma (wart) virus remains the only virus known to produce tumors in man. The possibility that the wart virus may cause more serious neoplasia in tissues other than skin cannot be discounted. Therefore, one objective will be to determine whether wart viral DNA sequences exist in cells derived from patients with various benign and malignant tumors. These will include laryngeal papillomas, mucosal papillomatosis, and other tumors such as nasopharyngeal carcinomas and connective tissue tumors. The experimental approach will be to analyze cellular DNA derived from various tumors for wart viral DNA sequences. For these studies "nicked" wart viral DNA will be labeled in vitro with labeled thymidine triphosphate and DNA polymerase to make a highly radioactive DNA probe. Detection of viral DNA sequences in diseased cells in some type of "carrier" state after onset of disease would be of great interest. The bovine papilloma virus appears to be the most oncogenic of the papilloma viruses. In order to study some of the relationships occurring between this virus and its host, BPV-transformed cell lines will be established and subsequently characterized. Specifically, we will examine transformed cell lines for viral and viral-induced antigens, BPV DNA sequences and BPV-specific mRNA.